RNA Epigenetics: Fine-Tuning Chromatin Plasticity and Transcriptional Regulation, and the Implications in Human Diseases

Abstract

Chromatin structure plays an essential role in eukaryotic gene expression and cell identity. Traditionally, DNA and histone modifications have been the focus of chromatin regulation; however, recent molecular and imaging studies have revealed an intimate connection between RNA epigenetics and chromatin structure. Accumulating evidence suggests that RNA serves as the interplay between chromatin and the transcription and splicing machineries within the cell. Additionally, epigenetic modifications of nascent RNAs fine-tune these interactions to regulate gene expression at the co- and post-transcriptional levels in normal cell development and human diseases. This review will provide an overview of recent advances in the emerging field of RNA epigenetics, specifically the role of RNA modifications and RNA modifying proteins in chromatin remodeling, transcription activation and RNA processing, as well as translational implications in human diseases.

The emerging roles of the interaction between m6A modification and c‐Myc in driving tumorigenesis and development

“…Among them, m6A modification has received great attention in cancer and has gained clinical significance (Chen, Wang, et al, 2021). m6A modification can affect the transcription, stability, and translation efficiency of c‐Myc through its regulators, namely writers, erasers, and readers, and thus plays a role in different types of tumors (Meyer & Jaffrey, 2014; Willbanks et al, 2021; Wood et al, 2021). We reviewed the specific effects of m6A regulators on c‐Myc from different perspectives, including the direct or indirect mode of action and different modification sites on c‐Myc mRNA.…”

Whole Exome Sequencing in a Population With Severe Congenital Anomalies of Kidney and Urinary Tract

“…Inappropriately folded proteins induce the Unfolded Protein Response which triggers a cytotoxic pathway, leading to apoptosis and impairment in cell function and structure ( 42 ). Additionally, NOP2/NSUN1 and NSUN2 are implicated in epigenetic modifications to create transcriptionally active chromatin ( 43 ). Due to the role of NSUN7 in epigenetic methylation of proteins, depletion of NSUN leads to diminished expression of the enhancer RNA of these proteins, especially ones that rely on cytosine modification ( 36 ).…”

Exploring the Epigenetic Regulatory Role of m6A-Associated SNPs in Type 2 Diabetes Pathogenesis

“…47 RNA methylation has been reported to regulate the entire mRNA metabolism process, including RNA stability, splicing, nuclear transport, translation, and degradation, thereby affecting the key biological functions in the regulation of different cellular processes. 48,49 Therefore, the expression of genes corresponding to m6A-SNPs may be affected. Experimental epitranscriptomic study conducted by Tian and his colleagues proved that overexpression of the rs8100241[A] (an m6A-SNP, G>A) allele significantly increased the level of ANKLE1 m6A and promoted the expression of ANKLE1 protein compared with that of rs8100241[G] allele.…”